The ion-sensitive field effect transistor (ISFET) is based on a MOSFET with a remote gate (or “reference electrode”) lying beneath a chemically-sensitive insulator. The surface of the insulator is exposed to an electrolyte upon which measurements are to be made. A typical ISFET use scenario is illustrated in FIG. 1. Field effects from ionic charge interaction at the insulator surface cause shifts in the ISFET drain current vs gate to source voltage (ID-VGS) characteristic as illustrated in FIG. 2. The insulator in contact with the electrolyte is chosen according to its chemical properties and sensitivity to a particular ion.
For ISFETs designed to measure the pH of an electrolyte, i.e. the H+ ion content of the electrolyte, silicon nitride and aluminium oxide membranes are commonly used to insulate the gate. ISFETs can be made sensitive to ions other than H+ through the choice of the ion-sensitive membrane, thus adding an element of ion-selectivity. ISFETs whose membrane is modified to be selective to a particular ionic species are known as ChemFETs, with a further variation, known as EnFETs, using enzymes in close proximity to the membrane surface. It has also been shown that even conventional pH-ISFETs with unmodified Si3N4 membranes exhibit a limited but measurable sensitivity to K+ and Na+ ions. This said, practical and commercial applications of the ISFET for applications other than pH sensing are rare. Nonetheless, in the following discussion, the term ISFET is used both specifically to refer to a pH sensor and generally to refer to all ion and enzyme sensitive FETs operating on similar principles.
The attractiveness of ISFETs and their FET-based counterparts is that they are compatible with the standard fabrication processes used to mass produce computer chips and can therefore be reliably and cost-effectively produced. Importantly, processing circuitry can be integrated onto the same chip as the ISFET device itself. The integration of intelligent circuitry with the sensing device itself is what is required for the development of so-called “smart sensors” which require robustness to non-ideal sensing conditions, as well as to provide electronics to discriminate between chemicals “on-chip”.
The normal operating mode of an ISFET is the strong inversion region of the ID-VGS characteristic. In this region, the gate to source voltage exceeds the threshold voltage VTH, resulting in a strong inversion of the channel underlying the gate. For this mode of operation, drain current is related to the gate voltage by a square law or linear relationship.
Referring again to FIG. 1, any voltage applied to the reference electrode of an ISFET is capacitively-coupled via the electrolyte to the insulator surface, where a pH-dependent charge from ions on this interface modulates the channel current, causing the observed shifts in the ISFET transfer characteristic, thereby modulating its threshold voltage Vth. Assuming that the ISFET is operated in the constant drain current mode, with a constant drain-source voltage, the gate to source voltage directly reflects the pH-sensitive interfacial potential at the gate interface, that is:pH=pHcal+Vgs/S,  (1)where pHcal is the pH of a calibration liquid at 37° C. and S is the pH sensitivity of the ISFET. The derivation of this relationship is detailed further in “ISFET, Theory and Practice”, P. Bergveld, IEEE Sensor Conference, Toronto, October 2003. However, this approach assumes a constant temperature, and in any practical approach temperature compensation must be applied.
The conventional approach to compensating measurements for temperature effects is to model the temperature dependence of a system, measure the temperature in parallel with the pH, and correct the measured pH on the basis of the model and the measured temperature. Whilst effective, this approach has a number of disadvantages. Firstly, it relies upon the provision of a temperature sensor, typically comprising a temperature sensitive resistor integrated onto the same chip as the ISFET. Secondly, processing power must be provided to perform the correction. Thirdly, the process of correcting the measured pH values takes time. In a typical system, pH and temperature values are converted into their digital equivalents, prior to carrying the further processing with a microprocessor or CPU. If necessary, digital control outputs are converted into analogue equivalents prior to application to a device to be controlled.
It has long been recognised that a key area in which ISFETs can be applied is that of implantable and wearable sensors. The requirements of conventional ISFET design outlined in the previous paragraph do not sit well with such sensors which require to be small, to consume low levels of power, and to be extremely accurate. Especially where the sensors form part of a control loop, e.g. controlling a drug delivery system, they must also be extremely accurate.